1,2,4-Triazol halkası taşıyan bazı üre ve tiyoüre türevleri ve anti-asetilkolinesteraz aktiviteleri

1,2,4-Triazol halkası taşıyan bazı üre ve tiyoüre türevleri ve anti-asetilkolinesteraz aktiviteleri Amaç: Yirmi adet farklı tiyoüre ve üre türevleri sentezlenmiş ve asetilkolinesteraz enzimini (AChE) inhibe etme yetenekleri Ellman’ın modifiye spektrofotometrik yöntemi ile değerlendirilmiştir. Yöntem: Anti-asetilkolinesteraz aktivite tayini Ellman’ın modifiye edilmiş spektrofotometrik yöntemi kullanılarak yapılmıştır. Bu spektrofotometrik yöntem bir kromojenik reaktif olan 5,5- dithiobis-(2-nitrobenzoik asit) ile salınan tiyokolinin renkli bir ürün vermesi esasına dayanır. Bulgular: Sentezlenen bileşiklerin (1a-e, 2a-e, 3a-e ve 4a-4e) anti-asetilkolinesteraz aktivite tayini Ellman’ın modifiye edilmiş spektrofotometrik yöntemi kullanılarak yapılmıştır. Test edilen bileşikler arasında, (4-{[(4-triflorometilfenil)karbamoil]amino} fenil)asetik asit (1d), en yüksek aktivite gösteren bileşik olmuştur. Bileşik 1d’nin 0.1mM konsantrasyonda inhibisyon oranı %48.55 olarak hesaplanmıştır. Sonuç: Anti-asetilkolinesteraz aktivite tarama sonuçları incelediğinde, fenil halkasının 4. konumunda triflorometil grubu taşıyan bileşik 1d’nin kaydadeğer anti-asetilkolinesteraz aktivite gösterdiği tespit edilmiştir. Aktivite sonuçları incelendiğinde, fenil halkası üzerinde halojen taşıyan yapıların anti-asetilkolinesteraz aktiviteyi arttırıcı yönde katkı sağladığı gözlenmektedir

Synthesis and biological evaluation of novel 1,3,4-thiadiazole derivatives as possible anticancer agents

The synthesis of new N-(5-substituted-1,3,4-thiadiazol-2-yl)-2-[(5-(substituted amino)-1,3,4-thiadiazol-2-yl)thio]acetamide derivatives and investigation of their anticancer activities were the aims of this work. All the new compounds’ structures were elucidated by elemental analyses, IR, 1H NMR, 13C NMR and MS spectral data. Anticancer activity studies of the compounds were evaluated against MCF-7 and A549 tumor cell lines. In addition, with the purpose of determining the selectivity of cytotoxic activities, the most active compound was screened against a healthy NIH3T3 cell line (mouse embryonic fibroblast cells). Among the tested compounds, compound 4y (N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-((5-(p-tolylamino)-1,3,4-thiadiazol-2-yl)thio)acetamide), showed promising cytotoxic activity against MCF7 cancer cell with an IC50 value of 0.084 ± 0.020 mmol L–1 and against A549 cancer cell with IC50 value of 0.034 ± 0.008 mmol L–1, compared with cisplatin. The aromatase inhibitory activity was evaluated for compound 4y on MCF-7 cell line showing promising activity with IC50 of 0.062 ± 0.004 mmol L–1

Synthesis and Antimicrobial Activity of 2-[2-(2,6-dichloro phenyl)amino]benzyl-3-(5-substituted phenyl-4,5-dihydro-1H-pyrazol-3-yl-amino)-6,8-dibromoquinazolin-4(3H)ones

A series of 2-[2-(2,6-dichlorophenyl)amino]benzyl-3-(5-substituted phenyl-4,5-dihydro-1H-pyrazol-3-yl-amino)-6,8-dibromoquinazolin-4(3H) ones 6a-m have been synthesized by the reaction of 2-[2-(2,6-dichlorophenyl)amino]benzyl-3-substituted phenylacrylamido-6,8-dibromoquinazolin-4(3H) ones 5a-m with hydrazine hydrate in the presence of glacial acetic acid. The chalcones 5a-m were prepared by the condensation of 2-[2-(2,6-dichlorophenyl)amino]benzyl-3-acetamido-6,8-dibromoquinazolin-4(3H)one 4 with different substituted aromatic aldehyde. The benzoxazinone 2 was synthesized from 2-[2-(2,6-dichlorophenyl)amino]phenyl acetyl chloride 1 on treatment with 3,5-dibromoanthranilic acid in pyridine, which on reaction with hydrazine hydrate and then on acetylation reaction yielded 4. The structures of these compounds have been elucidated by elemental analyses, IR, and NMR spectral data. The title compounds pyrazolyl-quinazolin-4(3H)ones 6a-m were evaluated for their antibacterial and antifungal activities in vitro

Synthesis of Some Oxadiazole Derivatives as New Anticandidal Agents

In this study, 5-[(pyrimidin-2-ylthio)methyl]-1,3,4-oxadiazole-2(3H)-thione (3) was synthesized via the ring closure reaction of 2-(pyrimidin-2-ylthio)acetohydrazide (2) with carbon disulphide. New oxadiazole derivatives 4a-f were obtained by the nucleophilic substitution reaction of compound 3 with various phenacyl bromides. The chemical structures of the compounds were elucidated by IR, 1H-NMR, 13C-NMR and FAB+-MS spectral data and elemental analyses. The newly synthesized derivatives 4a-f were tested in vitro by using a microbroth dilution method against C. albicans (clinical isolate, Osmangazi University, Faculty of Medicine, Eskişehir, Turkey), C. albicans (ATCC 90028), C. glabrata (clinical isolate, Osmangazi University, Faculty of Medicine, Eskişehir, Turkey), C. tropicalis (NRRL Y-12968), C. krusei (NRRL Y-7179), C. parapsilosis (NRRL Y- 12696), C. albicans (NRRL Y-12983), C. glabrata (clinical isolate, Anadolu University, Faculty of Science, Department of Biology, Eskişehir, Turkey). Among these compounds, compound 4a was found to be the most potent derivative (MIC = 0.007–0.06 versus ketoconazole: 0.001–0.007 mg/mL) against Candida species, except C. tropicalis and C. krusei when compared with the standard antifungal ketoconazole

Synthesis and evaluation of novel 2-[(1,2,4-triazol-3-yl)thio]acetamide derivatives as potential serum paraoxonase-1 (PON1) activators

Coronary artery disease and low-density lipoprotein (LDL) levels in the blood have long been known to be associated with peripheral vascular diseases. Paraoxonase-1 (PON1) enzyme is related to serum levels of high-density lipoprotein (HDL) and protects LDL from oxidation which may result in development of microvascular disease in diabetes. The enzyme has a major role in the prevention of atherosclerosis besides antioxidant properties. Additionally, PON1 is important in the detoxification of organophosphate insecticides from the body. In this study, we aimed to synthesize highly active new compounds which can be a drug candidate and evaluate their effects on PON1 activity. Nine novel triazole compounds bearing thioacetamide moiety (5a-i) were synthesized and their in vitro PON1 activity was investigated. The PON1 enzyme was purified from human serum using ammonium sulfate precipitation method. Also, it was further purified using Sepharose 4B-L-tyrosine- 1-naphthylamine affinity chromatography. Among the synthesized triazole compounds, 5b, 5c, 5f and 5h have been determined to increase PON1 activity, remarkably. Compounds 5b, 5c, 5f and 5h bearing 5-nitrothiazole, benzothiazole, 6-ethoxybenzothiazole and 6-florobenzothiazole moieties could be considered to proceed in vivo investigations which is a further stage for a drug candidate. © 2017, Marmara University. All rights reserved

Synthesis and Antimicrobial Activity Evaluation of New Benzimidazole—Thiazole Derivatives

Antibiotic resistance which was expedited by the use of antimicrobial drugs has been a significant global challenge for public health [1]. [...